System for timing the coagulation of blood

ABSTRACT

Sensitivity of a magnetically coupled mechanical blood clot timing system is increased by providing an adjustable source of steady and time varying magnetic flux lines which couple a ferromagnetic member immersed in the blood sample with a variable conductance device disposed adjacent to the test vessel. A relative motion is produced between the member and the vessel. A predetermined change in the conductance of the device is detected when the blood clots and there is a change in the magnetic flux lines. Stability of the system is improved by shaping the test vessel to permit free rotation of the member.

limited States Patent Mintz SYSTEM FOR TIMING THE COAGULATION 0F BLUOD Filed:

Appl.

Inventor: Michael D. Mintz, Edison Twp.,

Middlesex County, NJ.

Assignee: international Technidyne Continuation-impart of Ser. No. 19,003, March 2,

Pat. No. 3,695,842.

US. Cl, 23/259, 23/230 B, 23/253 R,

int. Cl. G0lln 11/10, GOln 33/16 Field of Search 23/259, 230 R, 230 B, 253 R;

References Cited UNITED STATES PATENTS 9/1962 Jewett 73/54 ANALYZER SYSTEM MAGNETIC ans ClRCUlT Sept. 17, 1974 3,492,096 l/l970 Hattersley 23/230 B 3,520,659 7/1970 Steinberg et al. 23/230 B Primary Examiner-Robert M. Reese [57] ABSTRACT Sensitivity of a magnetically coupled mechanical blood clot timing system is increased by providing an adjustable source of steady and time varying magnetic flux lines which couple a ferromagnetic member immersed in the blood sample with a variable conductance device disposed adjacent to the test vessel. A relative motion is produced between the member and the vessel. A predetermined change in the conductance of the device is detected when the blood'clots and there is a change in the magnetic flux lines. Stability of the system is improved by shaping the test vessel to permit free rotation of the member.

, 13 Claims, 5 Drawing Figures PAIIIIIIIIIE I IIIIII 3836333 .SHEET 1 [IF 2 ANALYZER SYSTEM MAGNETlC BIAS CIRCUIT A NALYZER SYSTEM MAGNETIC I 7' l l 7b CIRCUIT SYSTEM FOR TIMING THE COAGULATION OF BLOOD BACKGROUND OF THE INVENTION 1. A. Field of the Invention This invention relates to the field of art of the analysis of blood as it transforms itself from a liquid to a solidified mass commonly called a clot or thrombus.

2. B. Prior Art The present invention is a continuation in part of the invention of patent application .Ser. No. 19,003, filed March 12, 1970 and issued with amendments Oct. 3, 1972 as a U.S. Pat. No. 3,695,842 for A Method and System for Analyzing a Liquid, having the same applicant and assignee as the present invention. Such prior application describes in detail a magnetically coupled mechanical blood clot detection system wherein a variable conductance device is disposed adjacent to a zone containing the liquid and a member of ferromagnetic material is disposed within the zone. A circuit of magnetic flux lines is formed between the device and the member, and a relative motion is imparted between the zone and the member. A predetermined variation in the conductance of the device is detected upon change in the magnetic flux lines when the liquid transforms itself and the member is displaced. A signal is produced at the time the predetermined variation in conductance has been detected.

It is further described in the foregoing patent application that an additional magnet may be used to provide the variable conductance device with a magnetic bias and that such variable conductance device may be in the form of a magnetic reed switch, whereby the magnetic bias may be effective to adjust the sensitivity of such reed switch to displacements of the ferromagnetic member.

It is still further described in the foregoing patent application that the variable conductance device may have secured thereto pole extensions such that the ferromagnetic member is maintained in a predetermined initial position by means of magnetic forces between the member and such pole extensions.

SUMMARY OF THE INVENTION A system for automatically determining the time of occurrence of the transformation of blood from a liquid to a solidified mass or blood clot. A member of ferromagnetic material is disposed within a vessel containing the blood. A-magnetically sensitive variable conductance device is disposed adjacent to the vessel. Steady and time varying magnetic flux lines couple the member and the device through the walls of the vessel. A relative motion is produced between the vessel and the member. When the blood transforms itself the member is displaced from an initial predetermined position relative to the device resulting in a change in the magnetic flux lines. The conductance of the device is changed by a predetermined change in the magnetic flux lines. A chronographic instrument records the time of occurrence of the change in conductance.

Further in accordance with the invention the inner wall of the vessel may be shaped to facilitate free, stable rotational motion of the member relative to the walls of the vessel and projections therefrom.

DESCRIPTION OF THE DRAWINGS FIG. 1 illustrates a basic detection system including test vessel, variable conductance device, ferromagnetic member, magnetic biasing features, and analyzer system.

FIG. 2 illustrates a further embodiment of the invention of a differing shaped test vessel.

FIG. 3 illustrates an electrical block diagram of the magnetic bias circuit of FIGS. 1 and 2.

FIG. 4 illustrates an electrical block diagram of the analyzer systems of FIGS. 1 and 2.

BASIC DETECTION SYSTEM Referring now to FIG. 1 there is shown a basic system of detecting the occurrence of the transformation of blood from a liquid to a blood clot or thrombus. Tube 10 may be a glass or plastic cylindrical test tube with inner side wall 10a, inner bottom surface 1% and outer side wall 10c. A member 15 of ferromagnetic material is immersed in blood 12 and lies on the inner surface 10a-b of tube 10. When tube 10 is inclined with axis of symmetry at some angle, 60 for example, from the vertical, member 15 touches inner side wall 10a and inner bottom surface 10b.

A variable conductance device comprising magnetic reed switch l7v is located beneath tube 10 with metal reeds 1741-19 of switch 17 preferably parallel to member 15. Magnetic pole extensions 17c-d extend from reeds 17a-b to closely approach outer sidewall of tube 10 at points adjacent to the ends of member 15. A magnetic bias coil 161 of solenoidal form surrounds reed switch 17 with the internal magnetic flux lines produced thereby essentially colinear with reeds l7a-b.

In the foregoing mannera circuit of magnetic flux lines is formed between member 15, pole extensions l7c-d and reeds 17a-b through the inner and outer surfaces of tube 10. In the embodiment of the invention shown in FIG. 1 member 15 is a solid cylindrical element that may be characterized by a degree of permanent magnetization. Magnetic flux lines resulting from the combined magnetic source strengths of member 15 and coil 161 are effective to cause reeds 17a-b to close and remain closed with member 15 in its illustrated position.

In operation, switch 17 is maintained fixed or stationary and test tube 10 is rotated about its axis in the illustrated clockwise direction. As test tube 10 is rotated, member 15 rolls freely and remains substantially in its illustrated initial predetermined lowest position as a result of the forces of gravity and the magnetic attraction of member 15 to pole extensions 17c-d. In this manner there is produced a relative motion between the inner surface l0a-b of test tube 10 and member 15.

As the blood transforms itself from a liquid to a clot, mechanical and adhesive forces are formed by the solidified blood mass between member 15 and inner walls 10a-b of tube 10. When such forces are of sufficient magnitude to overcome the foregoing gravitational and magnetic forces, member 15 tends to rotate with tube 10 and is thereby caused to depart from its initial predetermined position.

As member 15 is displaced there is a resultant reduction in the magnetic flux lines which maintain reeds 17a-bclosed. When this displacement is sufficient and the reduction of magnetic flux lines has progressed to a sufficient degree, reeds 17a-b open. This opening of the reed switch is detected by an analyzer system in a manner later to be described.

The permanent magnetization of member 15 may not always be of sufficient magnitude to maintain reeds 17a-b closed when member 15 is in its initial predetermined position. In such case magnetic bias coil 161 may be energized by a steady electrical current from magnetic bias circuit 160 such that the combined flux strength of member 15 and of magnetic bias coil 161 is sufficient to maintain reeds 17a-b closed. On the other hand, this magnetic bias is not so strong as to maintain reeds 17ab closed when member 15 is displaced from its'initial position by a predetermined distance of half the inside diameter of the test tube 10, for example. By reversing the current in coil 161 the result ing magnetic flux may be effective to decrease the magnetic strength of member 15 in those cases where the permanent magnetization of member 15 provides an excessive magnetic flux.

Specifically it will be seen that the magnetic bias produced by a predetermined steady current in coil 161 is effective to adjust the opening sensitivity of switch 17 to predetermined displacements of member 15 relative to switch 17.

Due to a process of hysteresis the magnetization of member 15 and steady magnetic bias of coil 161 may not always be of sufficient magnitude to cause reeds 17a-b to close when member 15 is first placed in its initial position. In such case magnetic bias coil 161 may be energized by a short burst or pulse of current from magnetic bias circuit 160 such that a time varying magnetic bias is produced. The combined flux strength of member 15 and magnetic bias coil 161 is of sufficient magnitude to cause reeds l7a-b to close during such pulse of current. On the other hand, this magnetic bias pulse must not be so strong as to cause reeds 17a-b to close when member 15 is not within a predetermined distance of its illustrated initial predetermined position.

Specifically, a time varying magnetic bias produced by a predetermined current pulse in coil 161 is effective to adjust the closing sensitivity of switch 17 to the presence of member 15 within a predetermined distance from switch 17.

FIG. 2

Instead of being inclined from the vertical as shown in FIG. 1 the test vessel may be maintained in a vertical position with ferromagnetic member 15 disposed horizontally at the bottom. For example, as illustrated in FIG. 2 the test vessel 150 may have a substantially cylindrical shape with closed bottom 150d. A pivot 154 extends from bottom 150d into the interior of vessel 150. Member 15 is maintained in a horizontal position by the flattened portion 155 of pivot 154. Variable conductance device, reed switch 17 is located beneath vessel 150 with reeds 17a-b substantially horizontal and pole extensions 17e-f directed to approach the ends of member 15.

It will be recognized that the force of mutual magnetic attraction of pole extensions 17e-f and member 15 may not always be of magnitude sufficient to maintain member 15 in its illustrated initial predetermined position parallel to reeds 17a-.b. In this case an additionalmagnet 162 may be positioned between the bottom d of vessel 150 and reed switch 17 such that the mutual attraction of member 15 and magnet 162 maintains member 15 in its preferred predetermined position parallel to reeds 17a-b. A steady magnetic bias produced by current in coil 161 is adjusted to oppose the magnetic flux lines of magnet 162 in reed switch 17 thereby preventing reeds 17a-b from assuming or maintaining a closed condition due to the influence of magnet 162 alone.

When member 15 is then placed in its initial predetermined position it functions as a magnetic shunt, in that a portion of the lines of magnetic flux of magnet 162 is diverted from reeds l7a-b and caused to form a magnetic circuit between magnet 162 and member 15, through the bottom 150d of vessel 150. The resulting net magnetic flux lines in reeds 17a-b may be adjusted by controlling electrical current supplied to coil 161 by magnetic bias circuit 160, such that reeds l7a-b attain and maintain a closed condition as previously described.

In operation reed switch 17, pole extensions l7emagnetic bias coil 161 and magnet 162 are held stationary while vessel 150 is rotated in its illustrated clockwise direction. Member 15 is immersed in blood 12 and lies at the bottom of vessel 150 maintaining its preferred initial position parallel to reeds 17a-b due to its mutual attraction with magnet 162. There is thereby produced a relative motion between member 15 and the walls of vessel 150. Upon the transformation of the blood 12 from a liquid to a clot, mechanical and adhesive forces are formed between member 15 and the walls of vessel 150. When these forces are of sufficient magnitude to overcome the described magnetic force holding member 15 in its predetermined initial position, member 15 rotates with vessel 150 and is thereby angularly displaced relative to reeds 17a-b. Magnetic flux lines of magnet 162 which had previously been shunted through member 15 now seek to complete a magnetic circuit through reeds 17a-b of reed switch 17 in opposition to the flux lines produced by electrical current in coil 161. The net magnetic flux in reeds 17a-b is thereby reduced and reed switch 17 which had previously been closed is caused to open.

In the above described manner it may be seen that the system of magnetic reed switch 17, pole extensions 17e-f, magnetic bias coil 161 and magnet 162 may be defined as an integral variable conductance magnetic detector that is sensitive to angular displacements of member 15 relative to reed switch 17.

VESSEL 150 Referring now to FIGS. 2 and 2A there is shown a cylindrical vessel closed at a bottom end 150 that is comprised of a nonferromagnetic material such as glass or plastic. A pivot 154 extends from bottom 150d and elevates member 15 such that projections 152 do not interfere with the horizontal rotation of member 15 relative to the inner surface of vessel 150. A flattened portion of pivot 154 provides a base for the free stable rotation of member by reducing tendencies for member 15 to roll or slide off of pivot 154 due to external accelerations or gravitational forces. On the other hand, the diameter of flattened portion 155 is not so large as to provide excessive contact with member 15 which might induce substantial frictional resistance to the free rotation of member 15 within vessel 150. Projections 152 from the bottom 150d of vessel 150 provide means by which the transformed blood clot may be mechanically gripped to the inner surface and caused to rotate with vessel 150, where adhesive forces between the clot, member and the inner walls of vessel 150 are insufficient to overcome the previously described magnetic holding force.

In particular it will be seen that vessel 1511 may be a substantially cylindrical shaped container having a portion of its inner surface formed to permit essentially unrestrained rotational motion of a ferromagnetic member disposed therein and a plurality of projections from its inner surface formed to provide a mechanical grip on solidified blood, thereby inhibiting such blood clot from rotating relative to the inner surface of the vessel. It will be understood that such vessel may be formed as an integrally molded structure.

As illustrated in FIG. 2A vessel 150 may have a tight fitting stopper 156 to contain member 15 prior to analysis and blood 12 during analysis. Blood 12 will ordinarily be injected into vessel 150 through a thin diaphram 156a comprising the center portion of stopper 156. In order to facilitate blood sample injection stopper 156 is typically composed of a soft plastic or elastomeric material that may be easily penetrated by a hypodermic needle, low density polyethylene or plasticized PVC, for example. A vent hole 157 may be provided in diaphram 156 to permit escape of air during sample injection. The material comprising vessel 1511 will usually be of a hardness sufficient to prevent penetration by a hypodermic needle, such as glass or polystyrene, thereby to prevent accidental injury to the user during diaphram 156a penetration and blood sample injection.

The stoppered vessel 1511 of FIG. 2A may also contain premeasured reagents such as inert blood coagulation activators, diatomaceous earth or microscopic glass beads, for example. In order to prevent loss of such reagent prior to use, vent hole 157 may be a perferation of diaphram 156a made by the user just prior to blood sample injection.

MAGNETIC BIAS CIRCUIT 160 Referring now to FIG. 3 there is shown an electrical block diagram of an adjustable source of electrical energy for energizing the solenoid coil 161 of FIGS. 1 and 2, thereby to produce magnetic bias in a manner and for purposes previously described. In particular, a steady electrical current flows from constant voltage source 163 to magnetic bias coil 161 by way of adjustable electrical resistance 164 and conductor 167a. A pulse of electrical current may simultaneously flow from pulse voltage source 165 to coil 161 by way of adjustable electrical impedance 166 and conductor 1667b. For automatic operation, pulse voltage source 165 may comprise a periodic voltage generator such as a relaxation oscillator, for example. Alternatively, voltage pulses may be generated as required by momentarily depressing a switch connected in series to a constant voltage source or charged electrical capacitor.

ANALYZER SYSTEM FIG. 1 illustrates an electrical block diagram of an analyzer system of FIGS. 1 and 2. Electrical energy source 811 may be a battery electrically connected by way of conductors 81 and 71, low time holding switch 60 or reed switch 17 and conductors 69a, 70 and 69 to various functional components of the system, defined here to include chronometer 54, incubator 28, drive motor 45 and magnetic bias circuit 160. Low time holding switch 60 may be of a manual, electromechanical or electronic type and is normally open. Drive motor 45, coupled through suitable transmission means is effective to produce rotation of tube 10 or vessel 150 as illustrated in FIGS. ll and 2 respectively. Incubator 28 may serve to control the temperature of the blood sample. chronometer 54 provides timing register for determining the time interval reguired for the blood to transform itself from a liquid to a clot.

Operation of analyzer system 20 is usually initiated with tube 111 or vessel 150 remote from proximity to the variable conductance device, reed switch 17. When the blood sample is in a state ready for analysis, low time holding switch 60 is manually closed. The various functional components, including magnetic bias circuit 160, are thereby energized, and reed switch 17 is made sensitive to the presence of ferromagnetic member 15 by the resulting bias lines of magnetic flux, as previously described. The test vessel is thereafter placed in the position for analysis illustrated in FIGS. 1 or 2. As tube 10 or vessel 150 is rotated by drive motor 45, member 15 moves into its preferred predetermined initial position in proximity to reed switch 17. Reeds 17a-b thereupon close. Low time holding switch 60 is opened manually or electronically after the closing of switch 17, thereby providing uninterrupted electrical connection between electrical energy source and the various functional components of analyzer system When the blood sample 12 has transformed itself from a liquid to a clot and reeds .17a-b are caused to open, by processes previously described, electrical energy source 50 is cut off from the functional components of analyzer system 211, including chronometer 54. Thereafter the timing register of chronometer 54 displays a record of the time of such opening of reed switch 17. In particular, analyzer system 20 provides means for automatically detecting a predetermined change in the conductance of reed switch 17 and for recording chronographic information relating to the time of blood sample transformation from a liquid to a clot.

It has previously been shown that reed switch 17 may be made sensitive to the proximity of member 15 by bias lines of magnetic flux. With low time holding switch 60 open, such magnetic bias is produced by electrical energy from source 80 flowing to coil 161 by the way of magnetic bias circuit 160 and reeds 17a-b. When reed switch 17 opens, it becomes latched out by the absence of the required magnetic bias. Thereafter, reed switch 17 cannot be reclosedl even if member 15 is accidently returned to its initial predetermined position.

It will be understood that the detection of changes in the lines of magnetic flux which pass through tube 10 in FIG. 1 or vessel in FIG. 2 may be achieved by devices other than reed switch 17. For example, the embodiments of the invention illustrated in FIGS. 1 through 4 have alternating current analogs that utilize a differential displacement transformer as a variable conductance device. Substitution. of a magnetically sensitive solid state device in place of reed switch 17 may also be made without departing from the spirit of the invention.

It will be further understood that magnetic bias coil 161 may be of a form other than solenoidal and that it may be located in positions other than surrounding the magnetically sensitive variable conductance device. Such coil may be wound around one or both pole extensions 17e-f of reed switch 17, for example.

It will be still further understood that rotation of tube in FIG. 1 or of vessel 150 in FIG. 2 may be in a counter-clockwise direction as well as the illustrated clockwise rotation, or that such rotation may be of an oscillatory nature, having amplitude sufficient to produce the desired displacement of member relative to the variable conductance device, 360 degrees, for example.

In FIG. 2 the described relative motion between the inner surfaces of vessel l50 and member 15 may be produced by maintaining vessel 150 stationary and rotating the integral variable conductance device as well as by the illustrated rotation of vessel 150.

What is claimed is:

l. A system of timing the occurrence of the transformation of blood from a liquid to a clot comprising a vessel containing said blood,

a member of ferromagnetic material disposed within said vessel,

means for providing relative motion between said vessel and said member,

an independent source of magnetic flux lines,

variable conductance means magnetically coupled throughthe walls of said vessel to said member by way of said magnetic flux lines for varying the electrical conductance upon change in said magnetic flux lines when the blood transforms itself and said member changes position relative to said variable conductance means.

2. The system of claim 1 in which there is provided a permanent magnet disposed beneath said vessel thereby to provide a substantial magnetic force for maintaining said member in a preferred predetermined position relative to said variable conductance means.

3. The system of claim 1 in which there is provided means for recording said time of occurrence of the transformation.

4. The system of claim 1 in which said vessel comprises a nonferromagnetic cylinder closed at one end and having pivot means extending from said closed end to allow free stable rotational movement of said ferromagnetic member relative to the inner walls of said vessel.

5. The system of claim 4 in which there is provided means for gripping said transformed blood to said inner walls.

6. The system of claim 1 in which said independent source of magnetic flux lines comprises a coil,

an energy source connected to said coil for providing through said coil an electrical energy flow to produce said magnetic fluxlines, and

means for adjusting said energy flow through said coil.

7. The system of claim 6 in which said energy source is steady and said electrical energy flow is adjusted by said adjusting means to maintain said variable conductance means in a closed circuit condition by said magnetic flux lines with said member in a predetermined position relative to said variable conductance means.

8. The system of claim 6 in which said energy source varies with time and said electrical energy flow is adjusted by said adjusting means to cause said variable conductance means to attain a closed circuit condition by said magnetic flux lines with said member in a predetermined position relative to said variable conductance means.

9. The system of claim 6 in which said variable conductance means comprises reed switch means and said coil is solenoidal with said reed switch disposed in the center thereof.

10. A nonferromagnetic reaction vessel for containing a liquid in which the time it takes for blood to transform itself from a liquid to a clot is analyzed comprising said reaction vessel having bottom and inner surface,

a ferromagnetic member disposed within said vessel,

and

pivot means extending from said bottom to allow unrestrained rotational movement of said member relative to said inner surface.

11. The reaction vessel of claim, 10 in which said vessel and said pivot means comprise an integral molded structure.

12. The reaction vessel of claim 10 in which there is provided a stopper for containing said member and said blood within said vessel, said stopper having diaphram means for receiving hypodermic injection of said blood into said vessel.

13. The reaction vessel of claim 10 in which there is provided at least one member extending from said inner surface for gripping said clot to said inner surface, said extending member being positioned in said vessel to allow clearance for the movement of said ferromagnetic member. 

2. The system of claim 1 in which there is provided a permanent magnet disposed beneath said vessel thereby to provide a substantial magnetic force for maintaining said member in a preferred predetermined position relative to said variable conductance means.
 3. The system of claim 1 in which there is provided means for recording said time of occurrence of the transformation.
 4. The system of claim 1 in which said vessel comprises a nonferromagnetic cylinder closed at one end and having pivot means extending from said closed end to allow free stable rotational movement of said ferromagnetic member relative to the inner walls of said vessel.
 5. The system of claim 4 in which there is provided means for gripping said transformed blood to said inner walls.
 6. The system of claim 1 in which said independent source of magnetic flux lines comprises a coil, an energy source coNnected to said coil for providing through said coil an electrical energy flow to produce said magnetic flux lines, and means for adjusting said energy flow through said coil.
 7. The system of claim 6 in which said energy source is steady and said electrical energy flow is adjusted by said adjusting means to maintain said variable conductance means in a closed circuit condition by said magnetic flux lines with said member in a predetermined position relative to said variable conductance means.
 8. The system of claim 6 in which said energy source varies with time and said electrical energy flow is adjusted by said adjusting means to cause said variable conductance means to attain a closed circuit condition by said magnetic flux lines with said member in a predetermined position relative to said variable conductance means.
 9. The system of claim 6 in which said variable conductance means comprises reed switch means and said coil is solenoidal with said reed switch disposed in the center thereof.
 10. A nonferromagnetic reaction vessel for containing a liquid in which the time it takes for blood to transform itself from a liquid to a clot is analyzed comprising said reaction vessel having bottom and inner surface, a ferromagnetic member disposed within said vessel, and pivot means extending from said bottom to allow unrestrained rotational movement of said member relative to said inner surface.
 11. The reaction vessel of claim 10 in which said vessel and said pivot means comprise an integral molded structure.
 12. The reaction vessel of claim 10 in which there is provided a stopper for containing said member and said blood within said vessel, said stopper having diaphram means for receiving hypodermic injection of said blood into said vessel.
 13. The reaction vessel of claim 10 in which there is provided at least one member extending from said inner surface for gripping said clot to said inner surface, said extending member being positioned in said vessel to allow clearance for the movement of said ferromagnetic member. 